反应详情

A solution of N1-(4-(6-chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide (100 mg, 0.42 mmol, Example 4) in n-BuOH (3 mL) was treated with 2 M methylamine/THF (0.2 mL) and heated in a screw cap vial at 80° C. for 12 h. The mixture was concentrated and the residue purified by preparative HPLC using a gradient of MeOH—H2O containing 0.1% TFA. The fraction containing the product was lyophilized to give the title compound as a pale yellow solid (60 mg, 34%). 1H NMR (DMSO-d6) δ 10.58 (s, 1H), 10.36 (br s, 2H), 8.19 (br s, 1H), 7.76 (d, 1H, J=12.1 Hz), 7.64-7.62 (m, 2H), 7.36-7.27 (m, 2H), 7.15 (dd, 2H, J=8.8, 8.8 Hz), 5.95 (br s, 1H), 3.49 (s, 2H), 2.80 (s, 3H); MS (ESI+) m/z 414.16 (M+H)+.

1. temperatureheated in a screw
2. customcap vial at 80° C. for 12 h
3. concentrationThe mixture was concentrated
4. customthe residue purified by preparative HPLC
5. additionThe fraction containing the product